Klinisk institutt 2

Midtveisevaluering - Anna Berg



Molecular and imaging biomarkers in premalignant and malignant endometrial lesions relevant for improved diagnosis and treatment

Cancer of the corpus uteri is the most frequent gynecological cancer in developed countries, globally affecting more than 140, 000 new women each year. Around 80% will presents with endometrioid subtype (EEC), and complex atypical hyperplasia (CAH) is regarded this subtypes precursor. The observed increase in EEC and CAH has been linked to the obesity epidemic in the industrialized world. In our study we aim to improve the diagnostic stratification between premalignant and malignant endometrial lesions, and also increase the knowledge about malignant development, through comprehensive molecular characterization of endometrial lesions. We also aim to improve the preoperative staging of endometrial cancer through the use of imaging techniques like MRI and PET-CT.  Patients diagnosed with endometrial cancer or complex atypical hyperplasia at Hakueland University Hospital are included in this study. Molecular characterization have been assessed in fresh frozen tissue by whole-exome and Sanger sequencing, oligonucleotide gene expression and Reverse Phase Protein Arrays and further explored in formalin fixed tissues by immunohistochemistry and Fluorescent in Situ Hybridization. We found MRI to be superior to endocervical curettage (ECC) in the diagnosing of cervical stromal invasion (FIGO Stage 2); a better preoperative diagnostic may prevent overtreatment of patients. We have demonstrated PIK3CA mutations, PTEN loss and PI3K and KRAS activation to be early events in endometrial carcinogenesis. We also suggest Stathmin protein expression to be a marker for improved diagnostic distinction between premalignant and malignant lesions.